病毒学总论

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病毒的基本性状·病毒的结构和化学组成一.结构-nucleocapsid1.core基因组2.capsid抗原性-envelopeSpikes(刺突)---virus-encodedglycoproteinprotrudingfromlipidbilayer,whichareimportantforadsorptionandentryintothehostcell.二.化学组成与功能-病毒核酸1.SegmentedRNA:AfewvirusescontainsegmentedRNAgenome.Influenzavirus:7-8segmentsRotavirus轮状病毒:11segmentsHemorrhagicfevervirus:3segments2.InfectiousnucleicacidInfectiousnucleicacidispurifiedviralDNAorRNA(withoutanyprotein)thatcancarryouttheentiteviralgrowthcycleandresultintheproductionofcompletevirusparticlesinhostcells.SuchasthegenomesofdsDNAvirusesand+ssRNAviruses.3.Functions1)todirectthevirusreplication2)viralgenome(基因组):viralnucleicacidconteinsallgeneticinformationofthevirus.3)someofviralnucleicacidpossessinfectiousness--infectiousnucleicacid-病毒蛋白质viralattachmentproteins(VAP)能与宿主细胞表面受体结合的蛋白质称为病毒吸附蛋白,VAP与受体的相互作用决定了病毒感染的组织亲嗜性,如与红细胞结合的VAP称为血凝素hemagglutinin(HA).-脂类和糖脂质主要存在于包膜,有些病毒含少量糖类,以糖蛋白形式存在,也是包膜的表面成分之一。包膜的主要功能是维护病毒体结构的完整性,失去包膜的包膜病毒没有感染性。·病毒的增殖-病毒的复制周期1.Absorption病毒VAP宿主细胞的受体甲型流感病毒HA唾液酸HIVGp120CD42.Penetration–Endocytosis(naked),fusion(enveloped),直接穿入3.Uncoating–溶酶体酶4.Biosynthesis1)dsDNA2)+ssRNA3)retrovirus5.assemblyandrelease(组装DNA核,RNA质;释放裸露lysis,包膜budding)·病毒的遗传与变异一.基因突变Conditionallethalmutant:thevirusproliferationonlyoccurundercertainconditions.Temperature-sensitivemutant(tsmutant):permissivetemperature:28℃~35℃;nonpermissivetemperature:36℃~40℃tsmutant:attenuatedmutant(vaccinemutant)制作减毒活疫苗二.基因重组与重配1.Generecombination:Theexchangeofgenesbetweentworelatedviruseswhichinfectedthesamecell.2.Reassortment:exchangeofgeneticmaterialbetweentwosegmentedviruseswhichinfectedthesamecell.e.g.Influenzavirus:三.Interactionofviralgeneticproducts(non-heritablevariation)1.Complementation(互补作用):geneticproductionreactivationbetweentwoviruses(oneorbothofwhichmaybedefective)2.Phenotypicmixing(表型混合):progenyvirusesmaycontaincoatcomponentsderivedfrombothparents·病毒分类Subvirus:refertothekindofinfectiousfactorwhichissmallerthanvirus.1).viroid:--containRNAonly--associatedwithplantdisease.2).satellitevirus:--containRNA,capsid--needhelpervirus--associatedwithplantdisease.3).Prion:infectiousproteinparticales病毒的感染与免疫·病毒的致病作用一.病毒感染的传播方式HorizontaltransmissionVerticalinfection:1)rubellavirus风疹病毒2)humancytomegalovirus(HCMV)人巨细胞病毒3)herpessimplexvirus(HSV)单纯疱疹病毒4)hepatitisBvirus(HBV)乙肝病毒5)humanimmunodeficiencyvirus(HIV)人类免疫缺陷病毒二.病毒感染的致病机制1.cytocidaleffect杀细胞效应mainlyinnakedvirus,polioviruscytopathiceffecte(CPE):在体外实验中,通过细胞培养和接种杀细胞性病毒,经一定时间后,可用显微镜观察到细胞变圆、坏死,从瓶壁脱落等现象,称为致细胞病变作用。Thepresenceofthevirusoftengivesrisetomorphologicalchangesinthehostcell.Anydetectablemorphologicalchangesinthehostcellduetoviralinfectionareknownasacytopathiceffect.2.Steadystateinfection稳定状态感染usuallycausedbyenvelopedviruses.virusesareproducedfromtheinfectedcellsbutthecellsarenotkilledbytheprocess.(1)cellfusion(2)viralAgexpressionontheinfectedcell(targetcell)membranes3.Inclusionbody包涵体roundorirregular-shapedbodiesoccurringinthecytoplasmandnucleiofvirus-infectedcellssuchas:rabies狂犬病,smallpox天花,herpes疱疹,etc.4.Cellapoptosis细胞凋亡viruseshavethepotentialtoinitiateorstaytheonsetofprogrammedcelldeath.5.Integrationandcelltransformation基因整合与细胞转化integrationoftheviralgenomeintocellularDNA.SuchasHIV(Retroviruses);HPV(DNAvirus)细胞转化:Infectionwithoncogenicvirusescancausecellmalignanttransformation三.病毒感染类型PersistentviralinfectionVirusesexistinthebodiesforalongtime(>6monthes).1)latentinfection潜伏感染:Intheseinfection,theacutediseaseisfollwedbyanasymptomaticperiodduringwhichthevirusremainsinalatentstate.Whenthepatientisexposedtoanincitingagentorimmunosuppressionoccurs,reactivationofvirusreplicatonanddiseasecanoccur.Someexamples:HSV,VZVinfection2)Chronicinfection:慢性感染achronicviralinfectiontendstodevelopgraduallyandlastforweeks,months,orevenyears.viruscanbecontinuouslydetected.Someexamples:hepatitisB,hepatitisC3)Slowvirusinfection慢发病毒感染:Suchinfectionshaveaprolongedincubationperiod(yearsormorethantenyears),andaprotracted,progressiveclinicalcourse.Someexamples:AIDS(HIV);SSPE(measlesvirus);prionsdisease(prions).·抗病毒免疫免疫因素免疫机制巨噬细胞滤过血液中病毒颗粒,使被调理的病毒颗粒灭活,将病毒抗原提呈给T细胞IFN诱导细胞产生抗病毒蛋白,抑制病毒复制,在病毒感染早期其作用NK细胞释放TNF-α,TNF-β和TNF-γ,非特异性杀伤病毒感染的靶细胞,早期抗体中和抗体能阻止病毒吸附,有调理作用,主要对细胞外游离的病毒起作用T细胞Th1比Th2重要,CTL能同靶细胞表面的病毒抗原反应,杀伤靶细胞,清除细胞内病毒一.固有免疫·Interferon(IFN)anti-virus;anti-tumor;modifyimmuneresponsesMechanisms:IFNcombineswithspecificreceptoroncellsurface→Triggersignaltransmission→AVPgeneactived→AVPmRNAtranscribed→AVPsynthesis.AVPmainlyconsistsoftwocell-encodedenzymes:2,5-Asynthetase,proteinkinaseR(PKR);dsRNA2,5-Asynthetase2,5-A→activationofRnaseL→degradviralmRNAs→inhibitviralproteinsynthesis→inhibitionofviralreplicationdsRNAPKRactivationofPKR→phosphorylateeIF-2(inactivatingeIF-2)→inhibitviralproteinsynthesis→inhibitionofviralreplication二.适应性免疫Virusneutrilizingantibodies:neutrilizingantibodies--antibodiesformedagainstsomesurfaceantigensoftheviruses.Theycancanactonfreevirusesandneutralizetheinfectivityoftheviruses.Mechanisms:neutrilizingantibodiescanbindtothesufaceproteinsofthevirus,andinterferewiththeadsorptionofviruses.IgGIgMSIgA病毒感染的检查方法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